Toronto RCC Application: "From bench to bedside to curbside" The objective of this submission is to improve the clinical outcomes of critically ill patients who require resuscitation in the out-of-hospital setting. The proposal presents a plan to accelerate the translation of basic science discoveries from the laboratory to the "curbside" by setting up a dynamic infrastructure of scientists, paramedics, administrators, ethicists, and physicians who will develop and test innovative therapies. The specific aims of this proposal are: 1) To develop a multidisciplinary team of scientists with expertise in basic science, critical care, outcomes, medical error, knowledge translation, simulation, and clinical evaluative research who have the requisite skills to identify the most promising new therapies, to efficiently perform clinical trials to test these therapies, and then to translate these findings to the broader medical community. 2) To establish a partnership of teaching hospitals, University, and large regional Emergency Medical Services (EMS; Regional Land EMS and Provincial Air Ambulance Systems). This partnership serves a population of over 8 million with an annual call volume of over 800,000 including over 5,000 cardiac arrests and over 2,000 severely injured adult and pediatric trauma patients. These patients will form the catchment population to test specific resuscitation protocols in the context of a large multi-institutional network. 3) To use a unique mobile, paramedic-specific human patient simulator as a tool to test the feasibility of protocols, and train paramedics with respect to the therapeutic strategies that will be tested in the out-of-hospital setting. 4) To develop a program, which will train the next generation of investigators in research skills related to resuscitation medicine.